Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAKSVYV)

DOT Name Core histone macro-H2A.2 (MACROH2A2)
Synonyms Histone macroH2A2; mH2A2
Gene Name MACROH2A2
Related Disease
Colorectal carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Neoplasm ( )
Squamous cell anal carcinoma ( )
Advanced cancer ( )
UniProt ID
H2AW_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2XD7; 6FY5
Pfam ID
PF00125 ; PF16211 ; PF01661
Sequence
MSGRSGKKKMSKLSRSARAGVIFPVGRLMRYLKKGTFKYRISVGAPVYMAAVIEYLAAEI
LELAGNAARDNKKARIAPRHILLAVANDEELNQLLKGVTIASGGVLPRIHPELLAKKRGT
KGKSETILSPPPEKRGRKATSGKKGGKKSKAAKPRTSKKSKPKDSDKEGTSNSTSEDGPG
DGFTILSSKSLVLGQKLSLTQSDISHIGSMRVEGIVHPTTAEIDLKEDIGKALEKAGGKE
FLETVKELRKSQGPLEVAEAAVSQSSGLAAKFVIHCHIPQWGSDKCEEQLEETIKNCLSA
AEDKKLKSVAFPPFPSGRNCFPKQTAAQVTLKAISAHFDDSSASSLKNVYFLLFDSESIG
IYVQEMAKLDAK
Function
Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. May be involved in stable X chromosome inactivation.
KEGG Pathway
ATP-dependent chromatin remodeling (hsa03082 )
Necroptosis (hsa04217 )
Neutrophil extracellular trap formation (hsa04613 )
Alcoholism (hsa05034 )
Systemic lupus erythematosus (hsa05322 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [1]
Lung cancer DISCM4YA Strong Biomarker [2]
Lung carcinoma DISTR26C Strong Biomarker [2]
Neoplasm DISZKGEW Strong Biomarker [3]
Squamous cell anal carcinoma DISTY5YZ Strong Biomarker [3]
Advanced cancer DISAT1Z9 moderate Biomarker [4]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Core histone macro-H2A.2 (MACROH2A2). [5]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Core histone macro-H2A.2 (MACROH2A2). [16]
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14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Core histone macro-H2A.2 (MACROH2A2). [6]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Core histone macro-H2A.2 (MACROH2A2). [7]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Core histone macro-H2A.2 (MACROH2A2). [8]
Doxorubicin DMVP5YE Approved Doxorubicin affects the expression of Core histone macro-H2A.2 (MACROH2A2). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Core histone macro-H2A.2 (MACROH2A2). [10]
Ivermectin DMDBX5F Approved Ivermectin increases the expression of Core histone macro-H2A.2 (MACROH2A2). [11]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Core histone macro-H2A.2 (MACROH2A2). [12]
Selenium DM25CGV Approved Selenium increases the expression of Core histone macro-H2A.2 (MACROH2A2). [13]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Core histone macro-H2A.2 (MACROH2A2). [14]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Core histone macro-H2A.2 (MACROH2A2). [15]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Core histone macro-H2A.2 (MACROH2A2). [13]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Core histone macro-H2A.2 (MACROH2A2). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Core histone macro-H2A.2 (MACROH2A2). [18]
Propanoic Acid DM9TN2W Investigative Propanoic Acid decreases the expression of Core histone macro-H2A.2 (MACROH2A2). [19]
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⏷ Show the Full List of 14 Drug(s)

References

1 Deficiency of 15-LOX-1 Induces Radioresistance through Downregulation of MacroH2A2 in Colorectal Cancer.Cancers (Basel). 2019 Nov 11;11(11):1776. doi: 10.3390/cancers11111776.
2 Histone macroH2A isoforms predict the risk of lung cancer recurrence.Oncogene. 2009 Sep 24;28(38):3423-8. doi: 10.1038/onc.2009.26. Epub 2009 Aug 3.
3 Loss of histone variant macroH2A2 expression associates with progression of anal neoplasm.J Clin Pathol. 2016 Jul;69(7):627-31. doi: 10.1136/jclinpath-2015-203367. Epub 2015 Dec 10.
4 Expression and functionality of histone H2A variants in cancer.Oncotarget. 2014 Jun 15;5(11):3428-43. doi: 10.18632/oncotarget.2007.
5 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
6 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
7 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
8 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
9 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
12 Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
13 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
14 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
15 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
16 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
17 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
18 Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
19 Propionic acid induces mitochondrial dysfunction and affects gene expression for mitochondria biogenesis and neuronal differentiation in SH-SY5Y cell line. Neurotoxicology. 2019 Dec;75:116-122. doi: 10.1016/j.neuro.2019.09.009. Epub 2019 Sep 14.